Risk Stratification of Patients With Type 2 Long‐QT Syndrome Through Analysis of T‐Wave Morphology

Background Risk stratification in type 2 long‐QT syndrome remains challenging, as QT duration may not fully reflect all underlying arrhythmic vulnerability. We assessed whether an index derived from the T‐wave morphology is associated with cardiac events in a cohort with type 2 long‐QT syndrome. Methods We retrospectively and prospectively analyzed 54 genotype‐confirmed patients with type 2 long‐QT syndrome. T‐wave morphology in 8 independent leads was assessed using a warping‐based index, the T‐wave morphology variation (TMV) index, quantifying T‐wave morphologic changes from a general population‐based reference T‐wave. Association with the first lifetime occurrence of a cardiac event, including either syncope or the combined ventricular arrhythmia end point, was tested using univariate and multivariable Cox regression models. Results Using the 25th‐percentile threshold (TMV≤−18.41 ms), more negative TMV values indicating greater morphologic changes and a broader or delayed repolarization phase in the T‐wave signal relative to the control, as observed in lead I, were significantly associated with increased risk of cardiac event (hazard ratio HR, 3.505 95% CI, 1.673–7.341; P <0.001). The association remained significant after adjustment for corrected QT (HR, 2.92 95% CI, 1.111–7.676; P =0.03) and after additional adjustment for sex (HR, 3.375 95% CI, 1.256–9.067; P =0.016), and the T‐wave morphology combination score (HR, 4.061 95% CI, 1.369–12.046; P =0.012). Conclusions T‐wave morphology abnormalities, quantified using TMV , are associated with a higher risk of cardiac event s after adjustment for corrected QT prolongation, sex, and morphology combination score. TMV could complement current risk stratification strategies, although confirmatory validation in larger, independent, prospective cohorts is pending.